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You may have heard the term “non-disclosure” testing being thrown around, and are wondering what this means.

Non-Disclosure testing can be an option for individuals who are at risk of being affected by a late-onset disorder, such as Huntington’s Disease, Spinocerebellar Ataxia, etc., and do not wish to know their own genetic status, but would like to make sure that their children do not inherit this disease. People can react to this kind of information very differently, some wish to know, while others do not.

As the title states, non-disclosure involves keeping the at-risk individual’s status for a condition such as Huntington disease, for example, unknown. How can this be done, you may ask? Is it possible to test embryos for a condition that their parent may not even have? In fact, there are two different methods by which Non-Disclosure PGT can be performed. Complete non-disclosure needs to be maintained by the PGT lab and the patient’s IVF center for any kind of non-disclosure testing. This means that patients should not be provided with information regarding the number of eggs retrieved, number of embryos tested, or the number of embryos recommended for transfer. While this may be difficult for some to be without, it helps to avoid any potential deduction of genetic status based on the number or percentage of embryos with normal test results.

Once we have received the documentation from the at-risk individual’s family member, such as genetic test results from an affected parent, and confirmation of available family members to participate in the development of the testing system, we can then determine which method of non-disclosure testing might be feasible.

The first method by which non-disclosure PGT can be performed is called Indirect. Indirect Non-Disclosure testing is done by linkage analysis. Linkage analysis involves establishing the particular markers an individual shares with their parents. To review, with autosomal dominant conditions, such as Huntington Disease (HTT), an individual receives two copies of the HTT gene, one copy of the HTT gene from their mother and one copy of the HTT gene from their father. One affected copy of the HTT gene is sufficient to cause disease. Let’s say, for example, the at-risk individual’s mother is affected with Huntington Disease, this means that the mother has two copies of the HTT gene, one that is unaffected, and one that is affected, while the at risk individual’s father is unaffected, meaning he has two copies of the HTT gene that are unaffected. The at-risk individual inherited one of these healthy copies from their father. The at-risk individual has a 50% chance of inheriting their mother’s affected HTT gene copy and a 50% chance of inheriting their mother’s healthy HTT gene copy, but it is not known if they inherited the unaffected or affected copy of the HTT gene from their mother. RGI will select for embryos that inherit the at-risk individual’s paternal unaffected HTT gene copy, since we do not know if the individual’s maternal gene copy is healthy or affected. Our lab will only identify which of the at-risk individual’s HTT genes are maternal vs. paternal to select for embryos with the gene copy that comes from the individual’s father, which would be the healthy/unaffected copy. With this scenario, if the at-risk individual is unaffected with Huntington disease, meaning if they received the unaffected HTT gene copy from their mother, this means that healthy embryos may be selected against. Since our lab will only be testing for maternal/paternal linked markers, this ensures that nobody will know the at-risk individual’s status.

Direct Non-Disclosure is the second method of testing available, where we would send an anonymous DNA sample of the at-risk individual for testing at a separate clinical laboratory that specifically tests for the at-risk gene. This means that our PGT lab will receive the results from this outside testing and will know the at-risk individual’s genetic status. This information is not put into the patient’s medical chart and is not disclosed to anyone. With this method, PGT-A (testing for chromosomal abnormalities overall) is required. If the clinical testing for the at-risk individual comes back positive, our lab will test for both HTT and PGT-A. If the at-risk individual is negative, our lab will test only for PGT-A. However, whether PGT-M and/or PGT-A is performed will not be disclosed. The results will not reveal why certain embryos are not recommended for transfer (if an embryo is affected with Huntington disease or if it is aneuploid).  With this scenario, embryos are only selected against if they are affected with a genetic indication, either Huntington disease or a chromosomal abnormality.

We understand that this may be confusing or an overwhelming amount of information, so please feel free to reach out to us directly and we would be more than happy to walk you through it all!

Learn more about PGT testing for single gene disorders here: https://rgiscience.com/pgt-m/